Assessment of acute neurotoxicity of nitrogen-doped multilayer graphene nanoparticles and their capability to change Cd2+/Pb2+/Hg2+-induced injury in brain cortex nerve terminals

Abstract

Graphene materials are widely used in different technologies and certainly released into aquatic and air surroundings being environmental pollution components. Nitrogen‑doped graphene nanomaterials have great potential for application, in particular, in energy storage, as electrochemical sensors and waste water treatment. Aim. Evaluate neurotoxic risk of nitrogen-doped multilayer graphene. Methods. Here, nitrogen-doped multilayer graphene nanoparticles (N-MLG) were synthesized by means of electrochemical exfoliation of high-purity graphite rods in NaN3-based electrolyte and characterised using TEM, AFM and UV-vis spectroscopy. Neuroactive features of N-MLG were assessed in isolated cortex nerve terminals (synaptosomes) analysing the extracellular level of excitatory neurotransmitter L-[14C] glutamate and inhibitory one [3H]GABA. Results. It was revealed that N-MLG did not affect the extracellular synaptosomal levels of L-[14C] glutamate and [3H]GABA within the concentration range 0.01–0.5 mg/ml, and an increase in a concentration up to 1 mg/ml caused an insignificant increase (tendency to increase) in these levels for both neurotransmitters. To analyse a capability of interaction with heavy metals in biological system, N-MLG was investigated using model of acute Cd2+/Pb2+/Hg2+-induced neurotoxicity in nerve terminals. In was revealed that Cd2+/Pb2+/Hg2+-induced increase in the extracellular level of L-[14C] glutamate and [3H]GABA was not changed by N-MLG. Conclusions. N-MLG does not possess neurotoxic signs and is biocompatible within the concentration range 0.01–1 mg/ml. In biological system, N-MLG did not mitigate/aggravate Cd2+/Pb2+/Hg2+-induced neurotoxicity in nerve terminals.

Keywords

• nitrogen-doped multilayer graphene; nanoparticles; heavy metals; neurotoxicity; glutamate; gaba; brain nerve terminals